March 15, 2016
Researchers in Japan report that neural stem cells derived from readily available
T cell-derived iPSCs provide a neurological disease model when cultured in a
novel protocol developed by them. The findings are important for the treatment
of Parkinson's disease and are published in Stem
Cell Reports.
Neurological disease research, such as on Parkinson's disease,
relies on animal models and immortalized neural cell lines because the central
nervous system of patients is not accessible for invasive examination. Cultured
neural stem cells could provide an alternative that is closer to the biology of
the patient in question. However, due to the epigenetic memories of iPSCs,
efficient preparation of neural stem cells requires human induced pluripotent
stem cells (iPSCs) usually derived from skin fibroblasts harvested from patient
skin biopsies, which can lead to bleeding, scarring and infection. Now researchers
from a collaboration of universities and institutions in Japan have
demonstrated the potential efficacy of a less invasive alternative.
"T cells can be obtained non-invasively, are easily stored
and efficiently reprogrammed, and might therefore be an ideal source of
patient-specific iPSCs," explain Juntendo University's Wado Akamatsu and
Keio University's Hideyuki Okano, and colleagues in their latest report.
However the snag is that the source of stem cells seems to affect what cells
they are likely to differentiate into. T cells are a type of lymphocyte or
white blood cell and the researchers obtained very few neural cells from T
cell-derived iPSCs cultured in standard embryoid bodies compared with the usual
fibroblast-derived iPSCs.
To encourage differentiation into neural cells, the researchers
tried converting the iPSCs directly into neural stem cells as neurospheres -
culture systems of free-floating neural cells - instead of embryoid bodies that
contain cells of other germ layers. By using this protocol, T cell-derived
iPSCs efficiently differentiated into neural cells as well as
fibroblast-derived iPSCs. Neurospheres generated from T cell-derived iPSCs were
differentiated into neurons and various neuronal subtypes in similar quantities
to those from fibroblast-derived iPSCs.
Furthermore, the researchers confirmed that iPSCs derived from
the T cells of patients suffering from juvenile Parkinson's disease (PARK2)
exhibited impaired mitochondrial phenotypes that the team had previously
reported using the fibroblast-derived iPSCs derived from this patient.
"These results strongly support that the hiPSCs derived
from T-cells can be used as a model of neurological disease by using our
differentiation protocol," state Wado Akamatsu and Hideyuki Okano and colleagues
in their latest report.
Induced pluripotent stem cells (iPS cells or iPSCs) are
pluripotent stem cells that can be induced from somatic cells by cellular
reprogramming. The original set of reprogramming factors (so-called as Yamanaka
factors) are the genes Oct4 (Pou5f1), Sox2, cMyc, and Klf4. So far, it has been
reported that each of these factors can be functionally substituted by other
transcription factors, miRNAs, small molecules, or proteins.
Embryoid bodies
These are three-dimensional aggregates of embryonic pluripotent
stem cells. They contain the cells from all three germ layers and are readily
scalable because they form in suspension making them useful for culturing large
yields of cells. In contrast, the neurosphere culture used by Okano, Akamatsu
and collaborators are similar structures but comprising neural cells.
Parkinson's disease
In Parkinson's disease (PD), mutation of a specific gene is the
cause of PD (familial PD [FPD]) in approximately 10% of PD patients, whereas
the other 90% of patients are called sporadic PD. Particularly, understanding
the causes of sporadic PD may require statistical approaches that require large
numbers of cell lines, further raising the demand for less invasive approaches
to gathering neural cell models.
http://www.medicalnewstoday.com/releases/307929.php
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